EGR2 and NLRP3 Pathways in Obstructive Sleep Apnea-Related Cognitive and Mood Disorders

Condition(s) studied

Investigational drug(s) / intervention(s)

EGR2/NLRP3 pathway activity: Peripheral blood collection \& PBMC isolation: Children: 3 mL venous blood drawn from the right antecubital vein preoperatively; Adults: 3 mL fasting venous blood drawn the morning after PSG. Collected in EDTA tubes; PBMCs separated via Ficoll-Paque density gradient. Flow cytometry: 1×10⁶ PBMCs stained for CD14/CD16, HLA-DR, CD11b, CD80/CD86, CD163/CD206. RNA extraction: Remaining PBMCs lysed in TRIzol and stored at -80 °C for RT-qPCR of EGR2, NLRP3, and downstream genes Serum/plasma: Within 1 h of collection, centrifuge at 400 × g for 10 min at 4 °C; 1 mL used for ELISA quantification of TNF-α, IL-6, IL-1β, CCL2, IL-17, CRP; remainder stored at -80 °C for future proteomic or metabolomic assays Saliva sampling \& processing: 2-3 mL unstimulated saliva expectorated into sterile tubes, kept at 4 °C, processed (centrifuged, aliquoted) within 2 h, then stored at -80 °C.

fatty tissue: Subcutaneous fat biopsy (adults undergoing surgery): 100-200 mg obtained intraoperatively, placed in RNAlater at 4 °C for 24 h, then frozen at -80 °C for downstream RNA-seq, RT-qPCR, and Western blot analyses of EGR2, NLRP3, and related inflammatory markers

Study summary

Obstructive sleep apnea-hypopnea syndrome (OSAS) is a common disorder in which repeated airway blockages during sleep lead to low oxygen levels, inflammation, and disrupted sleep. Many OSAS patients-both children and adults-experience problems with memory, attention, and mood, such as anxiety or depression. However, the exact molecular drivers of these brain changes are not fully understood.

This observational study will enroll:

Children (ages 2-18) and adults (\>18 years) with OSAS, as well as age- and sex-matched healthy volunteers.

Clinical assessments: Children will undergo routine ENT examinations (including nasal endoscopy and X-rays); adults will have an overnight sleep study (polysomnography). All participants will complete questionnaires on sleepiness (e.g., ESS), mood (PHQ-9, GAD-7), and cognitive screening (MoCA for adults, age-appropriate scales for children).

Sample collection: A small blood draw (3 mL) and, when applicable (e.g., adults undergoing surgery), a tiny subcutaneous fat biopsy. Saliva samples will also be collected.

Laboratory tests:

Measure expression levels of two key inflammatory pathway genes-EGR2 and NLRP3-in blood cells, saliva, and fat tissue using RNA sequencing, RT-qPCR, and Western Blot.

Correlate these molecular markers with sleep parameters (AHI, oximetry), cognitive scores, and mood scores.

Data analysis: Develop and validate machine-learning models that integrate data from multiple tissues to predict who is at highest risk for cognitive or mood disturbances.

Eligibility

Primary outcome measure(s)

• Expression levels of EGR2 and NLRP3 in PBMCs, saliva, and subcutaneous fat tissue — Jul 2025 - Sep 2026
  Quantitative measurement of EGR2 and NLRP3 mRNA (by RNA-seq and RT-qPCR) and protein levels (by Western blot and ELISA) in peripheral blood mononuclear cells, saliva, and (when available) subcutaneous fat tissue collected at baseline. These molecular markers will be correlated with cognitive (MoCA) and mood (PHQ-9, GAD-7) scores

Trial sites (1)

More Xinhua Hospital, Shanghai Jiao Tong University School of Medicine trials in China

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